The ameliorating effects of low protein diets of high biologic value in the treatment of the uremic condition in human subjects are now well-documented. The improvement noted with this dietary procedure might be explained on the basis of a reduction in amino acid intake and subsequent catabolism and the assumption that amino acids or their metabolic products produce toxic symptoms in uremia. However, these toxic compounds have not been explicitly identified and there are limitations to studies with human subjects. It is proposed to produce uremia in rats by a two-stage surgical removal of kidney tissue. These animals will then be used as uremic models. Tissue enzyme concentrations, amino acid pools and catabolic rates of specific amino acids will be measured and compared to values obtained in sham-operated pair-fed control animals. An attempt will be made to determine whether the requirements for particular essential amino acids or for total dietary nitrogen are altered in the uremic rat by measuring weight maintenance in those animals with various intake levels of the amino acids. Studies will be conducted to assess the effects of dietary protein restriction in uremia and to determine whether one or more of the amino acids are related to the toxic symptoms of uremia by supplementation of the diet of these rats with single amino acids. If it can be established that only one or a few of the amino acids are associated with toxic symptoms, then the dietary treatment of uremia in human subjects might be radically altered.